PLSCR1 是一种细胞自主防御因子,可抵抗SARS-CoV-2 感染
Dijin Xu1,2,3,4, Weiqian Jiang1,2,3, Lizhen Wu3
1Howard Hughes Medical Institute, New Haven, CT, USA.
Nature
|July 12, 2023
概括
脂混杂酶1 (PLSCR1) 作为细胞自主防御对抗SARS-CoV-2,包括诸如Delta和Omicron的变种. 这种蛋白质通过向囊泡和防止融合来阻止病毒的进入,为抗病毒策略提供了一个新的目标.
科学领域:
- 免疫学
- 病毒学
- 细胞生物学
背景情况:
- 了解对SARS-CoV-2的保护性免疫力对于疫情准备和对抗变种至关重要.
- 虽然研究中和抗体,但局部细胞自主防御机制也至关重要.
- 之前的研究强调了宿主细胞在控制病毒感染方面的重要性.
研究的目的:
- 确定参与细胞自主防御SARS-CoV-2的宿主细胞因子.
- 调查脂混杂酶1 (PLSCR1) 在限制SARS-CoV-2感染中的作用.
- 阐明PLSCR1抑制病毒进入的机制.
主要方法:
- 在人类肺上皮和肝细胞中进行全基因组CRISPR-Cas9选.
- 干扰因子 (IFNγ) 刺激以诱导PLSCR1的表达.
- 使用活体SARS-CoV-2 (美国WA1/2020,三角形,欧米克朗BA.1) 和其他冠状病毒进行感染测试.
- 4Pi单分子切换纳米镜和双部分纳米报告仪测试.
- 在蝙蝠和小鼠中进行功能性保护研究.
主要成果:
- PLSCR1被确定为对抗SARS-CoV-2的强有力的细胞自主限制因子.
- IFNγ诱导的PLSCR1限制了多个SARS-CoV-2系和其他病原性冠状病毒.
- 影响了内细胞和TMPRSS2依赖的病毒进入路径.
- PLSCR1直接向病毒囊泡,防止尖端介导的融合和病毒逃逸.
- 阻断聚变的关键是PLSCR1的C终端β桶域,而不是其脂质混杂酶活性.
结论:
- PLSCR1是一种关键的宿主防御蛋白,在病毒进入后期抑制SARS-CoV-2.
- PLSCR1的机制涉及防止病毒囊泡与宿主细胞膜的融合.
- PLSCR1代表了开发新型抗冠状病毒策略的潜在治疗目标.
- 了解PLSCR1的功能很重要,特别是考虑到易受感染的个体的COVID相关突变.
更多相关视频
05:23Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
Published on: December 23, 2020
6.1K
10:16SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
Published on: January 6, 2017
7.4K
相关概念视频
The Antiviral System of Bacteria and Archaea: CRISPR
60
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats is a adaptive immune system found in bacteria and archaea that protects against viral infections. This system enables prokaryotic cells to identify, remember, and neutralize foreign genetic elements, primarily bacteriophages, by storing fragments of the invader’s DNA as a genetic memory.The CRISPR immune response begins during an initial infection. Cas (CRISPR-associated) proteins play a central role in this...
60
CRISPR and crRNAs
17.1K
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
17.1K
Rous Sarcoma Virus (RSV) and Cancer
5.1K
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
5.1K
Leaky Scanning
5.2K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.2K
Immune Response Against Viral Pathogens
828
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
828
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
